Should a 67-year-old male with mild erythrocytosis and thrombocytosis be referred to a hematologist (heme) for further workup or have additional labs such as B12 and iron levels ordered first?

Evaluation and Management of Mild Erythrocytosis and Thrombocytosis in a 67-Year-Old Male

Initial laboratory workup including B12, iron studies, and other basic tests should be completed before referring to hematology, as these can identify common reversible causes of mild erythrocytosis and thrombocytosis.

Initial Diagnostic Approach

For a 67-year-old male with mild erythrocytosis and thrombocytosis without smoking history or COPD, a systematic evaluation is necessary before specialist referral:

First-line Laboratory Tests

• Complete blood count with differential and peripheral smear review
• Serum ferritin, iron, TIBC, and transferrin saturation
• Vitamin B12 and folate levels
• Reticulocyte count and reticulocyte index
• Erythropoietin (EPO) level (critical for distinguishing primary vs. secondary causes) 1
• Comprehensive metabolic panel (including renal function)
• Inflammatory markers (ESR, CRP)

Interpretation of EPO Results

• Low EPO suggests primary erythrocytosis (potential myeloproliferative neoplasm)
• Normal or elevated EPO suggests secondary erythrocytosis 1, 2

Diagnostic Algorithm

1. Rule out relative erythrocytosis:

   • Check for dehydration
   • Repeat CBC after ensuring adequate hydration

2. If erythrocytosis persists:

   • Low EPO → Consider JAK2 mutation testing (for polycythemia vera)
   • Normal/high EPO → Evaluate for secondary causes (sleep apnea, renal disease, cardiopulmonary disorders)

3. For concurrent thrombocytosis:

   • Review peripheral smear for platelet morphology
   • Check iron studies (iron deficiency can cause reactive thrombocytosis)
   • Consider inflammatory markers to identify inflammatory causes

When to Refer to Hematology

Immediate referral to hematology is indicated if:

• JAK2 mutation is positive
• Erythrocytosis is significant (Hgb >18.5 g/dL in men)
• Thrombocytosis is significant (>600,000/μL)
• Abnormal peripheral blood smear suggesting myeloproliferative neoplasm
• Splenomegaly is present
• Symptoms of hyperviscosity exist (headache, visual disturbances)
• Family history of erythrocytosis or thrombocytosis 3

Defer referral until after basic workup if:

• Mild, asymptomatic abnormalities
• Clear secondary cause identified (e.g., iron deficiency causing reactive thrombocytosis)
• Normal EPO with identifiable secondary cause for erythrocytosis

Common Pitfalls to Avoid

• Accepting a single elevated value without confirmation on repeat testing
• Failing to check EPO level, which is crucial for differentiating primary from secondary causes 1
• Overlooking iron deficiency, which can cause reactive thrombocytosis while masking the degree of erythrocytosis 4
• Neglecting to consider medications that may cause erythrocytosis (testosterone, anabolic steroids)
• Premature referral to hematology before completing basic workup, which may delay diagnosis of common reversible causes

Clinical Implications

The combination of erythrocytosis and thrombocytosis raises concern for a myeloproliferative neoplasm, particularly polycythemia vera (PV) or essential thrombocythemia (ET). According to recent guidelines, these conditions require specific diagnostic criteria and risk stratification 5.

For PV, diagnostic criteria include elevated hemoglobin (>16.5 g/dL in men), bone marrow morphology showing hypercellularity, and presence of JAK2 mutation. For ET, criteria include persistent thrombocytosis >450,000/μL, bone marrow showing proliferation mainly of megakaryocytes, and presence of driver mutations (JAK2, CALR, or MPL) in approximately 90% of cases 5.

The initial laboratory evaluation will guide whether immediate hematology referral is needed or if treatable causes should be addressed first.